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Highlights d Representative sequencing (Rep-Seq) is a new method for tumor molecular profiling d Rep-Seq homogenizes residual tumor tissue not taken for standard pathology d Representative sampling of tumors generates accurate tumor mutation burden scores d Rep-Seq detects more mutations and accurately resolves clonal from subclonal variants

Sequencing of cell-free DNA (cfDNA) in cancer patients’ plasma offers a minimally-invasive solution to detect tumor cell genomic alterations to aid real-time clinical decision-making. The reliability of copy number detection decreases at lower cfDNA tumor fractions, limiting utility at earlier stages of the disease. To test a novel strategy for detection of allelic imbalance, we developed a prostate cancer bespoke assay, PCF_SELECT, that includes an innovative sequencing panel covering ∼25 000 high minor allele frequency SNPs and tailored analytical solutions to enable allele-informed evaluation. First, we assessed it on plasma samples from 50 advanced prostate cancer patients. We then confirmed improved detection of genomic alterations in samples with <10% tumor fractions when compared against an independent assay. Finally, we applied PCF_SELECT to serial plasma samples intensively collected from three patients previously characterized as harboring alterations involving DNA repair genes and consequently offered PARP inhibition. We identified more extensive pan-genome allelic imbalance than previously recognized in prostate cancer. We confirmed high sensitivity detection of BRCA2 allelic imbalance with decreasing tumor fractions resultant from treatment and identified complex ATM genomic states that may be incongruent with protein losses. Overall, we present a framework for sensitive detection of allele-specific copy number changes in cfDNA.

between clinically assisted hydration and lower rates or delayed onset of delirium. Conclusion There is insufficient evidence to draw conclusions on the impact of clinically assisted hydration on quality of life in the last days of life. Further research should focus on populations who are in the very final days of life. There is a lack of studies in non-cancer populations, and a lack of evidence relating to communication with patients and families about this uncertain area of clinical practice.

Aim Our multidisciplinary team quality improvement project aimed to ensure that all dying patients who experience TA have an effective individualised plan of care on an acute stroke ward (L21) within a tertiary centre. Background Leeds Teaching Hospitals was selected to be one of 10 hospitals to be part of the national 'Building on the Best Programme' in conjunction with Hospice UK, Macmillan, NHSE and NHSI. This was to build on what was already being achieved by hospitals to improve the quality of end of life care (EOLC). Often improvement work focuses on the management of pain and we wanted to focus on improving the care of patients with TA, a symptom found in up to 90% of dying patients, but not always focused on. Methods This work was led by the Palliative Care team in conjunction with the frontline team on L21. A driver diagram was produced to identify key areas of focus (FIG 1). Interventions included ward-based role modelling of expert care of the dying; (this included the recognition, assessment, care planning and evaluation of interventions for patients experiencing TA), ward-based teaching, display and presentation of improvement data and discussion of dying patients in safety huddles. Run charts were created for these initiatives, with baseline data pre-intervention and on-going data collection during the testing, implementation and sustainability phases. All interventions were developed following identification of gaps in care delivery/evaluation. Results Run charts (FIG 2-4) demonstrated statistically significant improvements in the rate of assessment, reassessment and evaluation of terminal agitation (p<0.05). Routine review and dissemination of data with the frontline teams in these initiatives enhanced collaborative engagement, motivation and success. Conclusion Through collaborative working and ward-based role modelling we have demonstrated it is possible to improve the overall management of this challenging symptom in terminal care. Background Taste or gustatory dysfunctions are implicated in loss of appetite, unintended weight loss, malnutrition and reduced quality of life. The benefits of Zinc supplementation for dysgeusia have been documented for the past 20 years with moderate quality supportive evidence available.Improvements in taste have been demonstrated in patients receiving chemoradiotherapy and in those with idiopathic taste loss. However, this approach does not appear to be part of routine practice. Aims We present a case study of a patient experiencing dysgeusia who was successfully treated with zinc supplementation and lifestyle changes. Case study description 60 year old patient with a uterine carcinoma receiving Sirolimus treatment. She described extreme taste sensation changes within 1 month of commencing the Sirolimus; foods tasted too salty with an accompanying overwhelming metallic taste. This severely impacted upon her enjoyment of food with reduced appetite, associated weight loss, fatigue and social withdrawal.Physical examination of the oral cavity showed no evidence of ...